Social Values and Health Priority Setting Case Study
Title of Case Study
Lapatinib for the treatment of advanced or metastatic breast cancer
Author
Sarah Clark
Author Contact
s.l.clark@ucl.ac.uk
Date of Submission
October 2012
Case Summary (approx. 350
words)
Lapatinib is a drug for treatment of patients with incurable cancer: they are at
the end of their lives. The case was considered in light of the ‘end of life’
criteria introduced by NICE in 2009, designed to be used when appraising lifeextending treatments for patients with short life expectancy, in order to take
account of the potentially higher cost of innovative interventions for small
patient groups with incurable conditions.
Please include information here about
why the case is of particular interest
At its first appraisal, the NICE Committee determined that lapatinib did not
qualify for all of the end of life criteria: whilst it met the requirements that the
patient population had a life expectancy of less than 24 months, and that is was
a small population (less than 7000), it did not meet the criteria for extending
life for more than 3 months. Thus end of life weightings could not be applied
to the ICER ratios for the drug, and it was judged not to be cost-effective for
use in the NHS.
At an appeal by the manufacturer against this point of the decision (amongst
others), the NICE Appeal Panel accepted the objection that the Appraisal
Committee’s interpretation of the 3 month life extension rule had been too
restrictive. It suggested that there could be ‘exceptional’ or ‘compelling’ cases
where the 3 month life extension criteria could be applied more flexibly,
although it did not state how ‘exceptional’ or ‘compelling’ should be defined.
On reconsidering lapatinib after this appeal, a second Appraisal Committee
decided that it qualified for all of the three end of life criteria, including that of
life extension. However, even with the end of life weighting, it judged that
lapatinib was still not a cost-effective use of NHS resources.
The case raises interesting general issues over the application of decision rules,
but also interesting specific issues around NICE’s end of life criteria and how
‘exceptional’ and ‘compelling’ cases might be defined in a patient group
which is already identified as being ‘exceptional’ and in ‘compelling
circumstances’.
1. Facts of the case
Please include information on as
many of the following as are relevant
to the case:
• At what condition is the
intervention, program or service
aimed?
• What are its effects? Eg. Is it
curative, preventative, palliative,
life-prolonging, rehabilitative?
Facts of the case
Lapatinib is a treatment for advanced or metastatic breast cancer. It has a
marketing authorization specifically for the treatment of patients whose
tumours overexpress the human growth factor receptors ErB1 and ErbB2 (also
known as HER1 and HER2) and who have progressive disease and have
already received prior interventions including anthracyclines, taxanes and
therapy with trastuzumab for metastases. Carcinoma of the breast which over
expresses ErbB2 (HER2) is associated with a worse prognosis and a shorter
life expectancy than other forms of breast cancer.
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• Is there a relevant comparator? If
so how does this intervention,
service or program compare to the
alternative? Include ICER
estimates/QALY costs if relevant.
• What are the significant features
about the condition and/or about
the patient population in this
case? Eg. patient population is
very young, very old, condition is
rare, life-threatening, life-limiting
etc.
• How are the benefits of the
intervention distributed across the
patient population and/or across
time?
• What is the cost or budget impact
of the intervention/service/
programme?
• What is the nature and strength of
the evidence about the outcomes
of the intervention, service or
programme? Eg. randomized
clinical trials, evidence on
patient-related outcomes.
• How did the issue about this case
arise - for example, from clinical
practice, from a policy setting,
from a topic selection process?
Clinical effectiveness
The manufacturer’s analysis included several different comparators including
capecitabine monotherapy, vinorelbine monotherapy, trastuzumab
monotherapy and trastuzumab combination therapy.
The manufacturer reported details of one randomised controlled trial. This
open-label trial enrolled women with HER2-overexpressing advanced or
metastatic breast cancer, who had received prior therapy, which included
anthracyclines, taxanes and trastuzumab in the advanced or metastatic setting.
Patients were randomised to receive treatment with lapatinib plus capecitabine
or capecitabine alone. 198 patients were enrolled in the lapatinib plus
capecitabine group and 201 patients in the capecitabine monotherapy group.
The primary outcome measure was time to progression, and the secondary
outcomes were overall survival, progression-free survival, overall tumour
response rate, clinical benefit rate and duration of response. Median time to
progression was reported as 27.1 weeks for lapatinib plus capecitabine
compared with 18.6 weeks for capecitabine monotherapy. Median
progression-free survival was reported as 27.1 weeks for the lapatinib plus
capecitabine group compared with 17.6 weeks for the capecitabine
monotherapy group. However, there was no statistically significant difference
in median overall survival: 67.7 weeks for lapatinib plus capecitabine and 66.6
weeks for capecitabine monotherapy.
Cost
The cost of lapatinib treatment is £57.45 per day, or £20,969 per year. The cost
of a 21-day cycle of capecitabine treatment is £244.00 per cycle or £4238 per
year. This gives a combined cost of lapatinib plus capecitabine of
approximately £25,207 per year.
Cost effectiveness
There are various estimates of cost-effectiveness, according to the different
comparators, as follows:
•
The ICER of lapatinib plus capecitabine compared with vinorelbine
monotherapy gave an ICER of approximately £79,000 per QALY
gained.
•
The ICER for lapatinib plus capecitabine in comparison with
trastuzumab monotherapy was approximately £24,000 per QALY
gained, but this did not take into account the comparison of
trastuzumab with capecitabine (trastuzumab is usually used in
combination with capecitabine) for which the ICER was
approximately £109,000 per QALY.
The manufacturer also used a ‘blended comparator’, which weighted
the costs and QALYs of all of the lapatinib comparators (that is,
capecitabine-, vinorelbine- and trastuzumab-containing regimens) to
produce a single ICER of approximately £61,000 per QALY gained
for lapatinib plus capecitabine in comparison with all comparators.
(NICE, 2009a)
•
2. Policy decision: process
Policy decision: process
Please include information on as
many of the following as are relevant
Lapatinib was appraised using NICE’s Single Technology Appraisal process.
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to this case:
• What stages/institutions were
•
•
•
•
•
•
•
involved in the decision making
process?
Is legal context important in this
case? If so, in what way?
Who was involved? Eg. key
stakeholders, the public,
professionals, industry, patients,
governmental or non-government
policy actors.
How were they involved, and at
what stages of the process?
Was there disagreement between
any of the parties involved in the
decision process?
Do any rules or frameworks exist
to guide decision making? If so,
were they followed in this
instance?
Do mechanisms exist for
challenging the decision at any
stage of the process?
How, if at all, is the decision
process or the decision itself
publicized?
3. Policy decision: content
However, there were a number of appeals from the manufacturer,
GlaxoSmithKline (GSK). As such, the timeline of the appraisal process was
as follows:
January 2009: The appraisal of lapatinib was considered at a fourth meeting
of the Appraisal Committee
March 2009: The first Final Appraisal Decision (FAD) was issued.
June 2009: The hearing of GSK’s appeal to NICE in respect of the first FAD.
This appeal was on several grounds of procedural unfairness of NICE’s,
including NICE’s ruling out of the use of trastuzumab as a comparator, and the
timing of announcements on the introduction of the end of life criteria, as well
as on what GSK suggested was an overly restrictive interpretation of the end
of life criteria - notably the 3 month life extension element (see
GlaxoSmithKline Notice of Appeal, 8 June 2009; see also Discussion section,
below)
July 2009: The decision of the Appeal Panel was issued; the Panel found in
favour of GSK on one point of appeal and a second point of appeal in part,
with both points relating to the application of the new Guidance on End of Life
Treatments. The appraisal was therefore returned to the Appraisal Committee.
September/October 2009: The fifth meeting of the Appraisal Committee took
place and a second negative Appraisal Committee Decision was issued on 21
October 2009.
November 2009: The sixth meeting of the Appraisal Committee to consider
this appraisal took place.
December 2009: A draft Final Appraisal Determination was sent to the NICE
Guidance Executive, who requested that the Appraisal Committee should give
further consideration to the appraisal in the context of potential cost savings to
the NHS if lapatinib were used in place of trastuzumab-containing regimens.
February 2010: The seventh meeting of the Appraisal Committee took place.
May 2010: The final (and currently applicable) FAD is issued recommending
that lapatinib does qualify for application of end of life criteria, but that it does
not provide sufficient benefits to justify its costs and therefore remains
unsuitable for use in the NHS.
Policy decision: content
Please include information on as
many of the following as are relevant
to this case:
Clinical effectiveness
The Committee discussed the clinical effectiveness of lapatinib plus
capecitabine presented in the main RCT. It noted that lapatinib plus
• What decision was made about the capecitabine was associated with an improved time to progression,
intervention, service or program, if progression-free survival and other secondary outcomes compared with
any?
capecitabine monotherapy.
• What values were relevant in the
case or in the decision itself? For
example, values of costeffectiveness, clinical
effectiveness, justice/equity,
solidarity or autonomy. How did
they affect the decision itself?
• Was the way in which these values
were balanced affected by any
specific features of the case? For
example, end of life
considerations, age of patients,
Cost effectiveness
The ICER of lapatinib plus capecitabine compared with vinorelbine
monotherapy gave an ICER of approximately £79,000 per QALY gained.
The Committee specifically considered the estimates of cost effectiveness that
included the patient access scheme comparing lapatinib plus capecitabine
against capecitabine and vinorelbine monotherapy. The Committee noted that
the ICERs were approximately £70,000 and £55,000 per QALY gained,
respectively.
The Committee noted that the ICER for lapatinib plus capecitabine in
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impact on carers, disease severity,
innovative nature of the
intervention, social stigma or
cultural sensitivity?
• Did the case challenge established
guidance or ‘decision rules’? Eg.
on cost-effectiveness, cost
thresholds, age discrimination etc.
If so, in what way?
• Were any health system-wide
considerations influential in the
decision? For example,
displacement of old technologies,
professional practice issues, or
infrastructure/feasibility
considerations.
comparison with trastuzumab monotherapy was approximately £24,000 per
QALY gained, but that this did not take into account the comparison of
trastuzumab monotherapy with capecitabine for which the ICER was
approximately £109,000 per QALY gained. The Committee considered that,
although the analysis presented by the manufacturer suggested that lapatinib
plus capecitabine compared with trastuzumab-containing regimens was cost
effective in the base case, the incremental analysis demonstrated that it was
based on a comparison of capecitabine with trastuzumab which was not cost
effective. The Committee was mindful that there was uncertainty about the
effectiveness of trastuzumab-containing regimens, but considered that even if
future evidence on the effectiveness of trastuzumab plus capecitabine
demonstrated that it was more cost effective than had been assumed, this
would only increase the ICERs for lapatinib plus capecitabine in comparison.
Therefore, the Committee concluded that the results of the manufacturer’s
cost-effectiveness analysis in this situation were unsupportable, and the
Committee could not, on this basis, recommend lapatinib plus capecitabine as
a cost-effective use of NHS resources.
The Committee also examined the economic analysis from the manufacturer
that used a blended comparator, which weighted the costs and QALYs of the
lapatinib comparators (that is, capecitabine-, vinorelbine- and trastuzumabcontaining regimens) to produce a single ICER of approximately £61,000 per
QALY gained for lapatinib plus capecitabine in comparison with all
comparators included in the economic analyses. The Committee was not
persuaded that it was appropriate to combine independent health technologies
to produce a single estimate of cost effectiveness nor that the economic
analyses that compared lapatinib plus capecitabine with a blended comparator
were appropriate. Specifically the Committee was not persuaded that it was
acceptable to include treatments in the blended comparator approach which,
when considered individually, were not cost effective. Therefore, the
Committee did not consider that the cost-effectiveness analyses using a
blended comparator could form the basis of a decision on the appropriate use
of NHS resources.
Patient Access Scheme
The Committee noted that the proposed patient access scheme (section 3.18)
had been applied to the blended comparator. The Committee was aware that
the manufacturer proposed to pay for the costs of lapatinib for the first 12
weeks of treatment for all people eligible for treatment, as part of this scheme.
The Committee recognised that the patient access scheme reduced the ICER,
using the blended comparator, from approximately £61,000 per QALY gained
to approximately £16,000 per QALY gained. The Committee did not consider
that applying the patient access scheme to the blended comparator was
appropriate because of its views on the acceptability of the blended comparator
as an appropriate basis for making recommendations about the cost
effectiveness of lapatinib
Other benefits
The Committee considered the wider benefits that may be associated with
lapatinib. These include providing a range of technologies for the treatment of
advanced or metastatic breast cancer and the fact that lapatinib is taken orally.
The Committee recognised the importance of patient choice, but considered
that lapatinib could not be recommended in the absence of evidence of cost
effectiveness. Therefore, the Committee was not persuaded that the benefits
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associated with the mode of administration of lapatinib or the importance of
patient choice should alter their decision about lapatinib being an appropriate
use of NHS resources.
(NICE 2009a)
End of life considerations
In the first appraisal determination (NICE, 2009a) - that is, before
GlaxoSmithKline’s first appeal - the following is the Committee’s assessment
of whether the end of life criteria apply to lapatinib:
•
The Committee understood that the main RCT reported a median
overall survival for patients receiving capecitabine monotherapy of
approximately 15 months (65.9 weeks) and, thus, it met the criteria for
short life expectancy.
•
It is estimated that approximately 2000 patients with HER2overexpressing metastatic breast cancer per year are receiving secondor third-line chemotherapy and are therefore eligible to be offered
treatment with lapatinib. In this respect lapatinib met the criteria for
small patient population.
•
The Committee observed that the trial data suggested that lapatinib
plus capecitabine extends survival relative to capecitabine alone.
However, it noted that the main RCT reported a gain in overall
survival of approximately 1.9 months which did not reach
conventional levels of statistical significance.
•
The Committee was also mindful of the results from the economic
model, but noted that this provided an estimate of life years gained of
0.19 reflecting a gain in overall survival of approximately 2.3 months.
Therefore, the Committee did not consider that the size of the possible
benefit was in keeping with the supplementary advice from NICE for
consideration of life-extending, end-of-life treatments.
•
The Committee was not persuaded that lapatinib fulfilled the criteria
for consideration of end of life treatments, and it concluded that the
use of lapatinib was not a cost effective use of NHS resources, and
recommended that lapatinib should only be used in the context of
further research.
However, consideration of the end of life criteria in relation to lapatinib
changes in the second appraisal determination issues in May 2010: the
Committee decides that all of the end of life criteria, including that of life
extension (the only criteria not accepted in the first appraisal in 2009, and one
of the points of appeal by GSK) are applicable to lapatinib. However it judges
that, even with the application of the end of life weights, the ICER ratio of
lapatinib of £54,900 (revised in light of new evidence from GSK) remains too
high.
The following is the relevant section of the second appraisal (NICE, 2010) in
respect of the life extension criteria and final judgement of ICER ratios:
“The Committee then considered the updated survival data provided by
the manufacturer and the alternative analyses that adjusted for crossover
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and baseline prognostic factors. The Committee noted that the revised
unadjusted estimate of overall median survival benefit was 2.4 months.
The alternative analyses, variously adjusting for crossover and baseline
prognostic factors, gave estimates in the range of 2.7 to 4.3 months. The
Committee noted that where presented the confidence intervals were
wide, extending down to 1 month or less.
The Committee heard from the DSU that it considered that the methods
used to adjust for crossover may have led to some bias in the estimates
and that there were alternative methods that might be more valid and
might give different estimates. The Committee was not therefore
persuaded that the adjusted estimates of overall survival presented by the
manufacturer led to estimates that were any more valid than the
unadjusted estimate of 2.4 months, and certainly did not provide robust
evidence that the extension of life provided by lapatinib was 3 months or
greater. However, the Committee noted that there was a minor chance
that lapatinib plus capecitabine might offer an increase in overall survival
of 3 months compared with capecitabine alone. It therefore concluded
that it should consider the ICERs presented by the manufacturer in light
of the end-of-life considerations.” (NICE, 2010; para. 4.21)
The Committee considered the further revised economic evaluation
presented by the manufacturer. The Committee noted that the ICER in the
further revised base case, including the patient access scheme, was
£59,400 per QALY gained. The Committee also noted that the modelled
overall survival benefit from lapatinib treatment in the further revised
base case was 3.5 months. The Committee discussed the extra weight that
might be considered acceptable for a potential increase in life expectancy
of 3 months taking into account the unique and innovative aspects of
lapatinib, patient need, and previous appraisals where judgements were
made taking into consideration the end-of-life supplementary advice, to
allow the cost-effectiveness estimates to fall within the range that is
normally accepted as a cost effective use of NHS resources.
The Committee concluded that the magnitude of additional weight that
would need to be assigned to the QALY benefits for the base-case ICER
of £59,400 per QALY gained to fall within the current threshold range
was not acceptable. The Committee further concluded that the magnitude
of greater weight that would need to be given to the QALYs gained in the
later stages of terminal disease, using the assumption that the extended
survival period is experienced at the full quality of life anticipated for a
healthy person of the same age, was also not acceptable.” (NICE, 2010;
para. 4.23)
4. Discussion
Discussion
Please use this space to reflect on, for
example:
An interesting issue arose in this case around the interpretation of the life
extension element of the end of life criteria.
• The reasons or values explicitly
used in making the decision. Do
these reflect any institutional
decision rules or statements of
value, for example commitments
to equality, non-discrimination or
fairness? Do they reflect wider
social, moral, cultural, religious
This was one of the main points in GlaxoSmithKline’s appeal against NICE’s
first appraisal determination, and it seems to have influenced the way in which
the Appraisal Committee considered the applicability of the life extension
criteria, as reflected in the second appraisal determination (NICE, 2010; see
excerpts from paras. 4.21 and 4.23 above).
The following is the relevant section of the appeal by GSK in response to the
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values, and if so how?
• Considerations not explicitly taken
into account in the decision, but
which may nonetheless have been
important ‘background’ factors.
These might include, for example,
public opinion, political
sensitivity, moral sensitivity, and
international reputation, as well as
cultural, social, moral, religious or
institutional norms.
• The impact of the decision making
process on the decision itself, if
any.
• Any issues relating to
implementation. For example,
whether access may be restricted
by capacity issues, even if the
intervention, service or
programme is provided on a
‘universal’ basis.
• Anything else you think
significant or interesting about the
decision.
first appraisal determination (it is worth quoting in full, but note particularly
point 2, later referred to in the Appeal Hearing as the ‘proportionality
argument’):
“GSK believes that the way in which NICE’s Supplementary Advice was
applied by the Appraisal Committee, in the context of its consideration of
lapatinib at paragraphs 4.19 - 4.21 of the FAD, was unfair.
In particular the criteria listed in NICE’s Supplementary Advice include a
requirement that the treatment should offer “an extension to life, normally of at
least an additional 3 months, compared with current NHS treatment”. The
way in which this criterion was interpreted by the Appraisal Committee in the
appraisal of lapatinib was highly restrictive; the Appraisal Committee
concluded, at paragraph 4.19 of the FAD that the trial data for lapatinib offered
an overall survival advantage of 1.9 months compared with capecitabine alone,
which did not reach conventional levels of statistical significance and that,
accordingly, the size of the possible benefit was not in keeping with NICE’s
Supplementary Advice. The Appraisal Committee therefore seemingly
considered that no further consideration of the Supplementary Advice was
required in the context of the appraisal of lapatinib. This was unfair for the
following reasons:
1. An inflexible application of the requirement that a treatment should extend
life by at least three months is inconsistent with NICE’s procedures: the
Supplementary Advice provided only that this should “normally” be the case.
2. In addition, an inflexible approach also fails to take into account the very
variable life expectancies that may be encompassed within a category of
patients who have less than 24 months to live. By way of example, where a
patient has only three months to live, a doubling of that life expectancy
arguably represents a greater treatment benefit than an extension of life of
three months in a patient who, in the absence of treatment, could expect only
23 months of life. The median survival in the capecitabine monotherapy arm
of the pivotal lapatinib trial in this indication was 15 months. The fact that an
extension of life of approximately two months from 15 months (the position in
the lapatinib trial) is proportionate to an extension of life of three months from
24 months (as provided in NICE’s Supplementary Advice) has not seemingly
been considered by the Appraisal Committee at all. In fact, where patients who
have received fewer than three chemotherapy regimens are considered, as
submitted for consideration by the Appraisal Committee on 21 January 2009, a
lapatinib containing regimen produces a median survival advantage of 32.2
weeks, over twice the three month period specified by NICE in its
Supplementary Advice.
3. The criticism by the Appraisal Committee that the survival advantage
associated with lapatinib in the pivotal trial in this indication did not reach
conventional levels of statistical significance (paragraph 4.19 of the FAD),
failed to take account of the fact that recruitment to the trial was halted early as
a result of the superior results associated with lapatinib treatment. The
Committee noted, at paragraph 3.2 of the FAD, that enrolment to study
EGF100151 was discontinued in view of the emerging data showing increased
time to disease progression (the primary endpoint) associated with lapatinib
therapy. It was deemed unethical to continue the study in light of this positive
benefit seen with the use of lapatinib. Accordingly, the study may have been
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underpowered to detect certain secondary endpoints (such as overall survival)
and subject to confounding as a result of cross over from the capecitabine arm
of the study (paragraph 3.4 of the FAD). Paradoxically, therefore, it is by
virtue of lapatinib’s proven superior efficacy that it has not been possible to
demonstrate a statistically significant improvement in overall survival. It is
clearly unfair that the most effective treatments, with the best early trial
results, are less likely to satisfy NICE’s criteria for more flexible consideration
by the Appraisal Committee.
4. NICE’s Supplementary Advice does not consider the additional costs
associated with prolonging life in patients who will live only a short time excluding the costs of the technology under consideration - and this has not
been taken into account by the Appraisal Committee in the context of this
appraisal. Almost invariably, a patient with a short life expectancy will require
additional health and/ or social services support in terms of nursing care,
medical consultations, hospital costs and the costs of medicines that alleviate
symptoms - before the costs of health technologies directed towards the
disease under consideration are considered. Therefore the survival benefits
associated with lapatinib treatment affect the assessment of cost-effectiveness before any costs associated with the drug itself are considered. Even if
lapatinib is provided at zero cost the cost utility ratio in comparison to
capecitabine alone is still £11,000/QALY - i.e. employing NICE’s
methodology, the very benefits associated with use of lapatinib, mean that it
appears less cost effective than a comparator.”
(GlaxoSmithKline Notice of Appeal, March 2009)
The response by the NICE Appeal Panel was as follows (NICE, Appeal
Hearing on Lapatinib, July 2009):
“As regards the ‘proportionality argument’, the Appeal Panel found that the
Committee's approach was correct. The amount of life extension required by
the Supplementary Policy is not to be varied relative to the overall life
expectancy of the patients in question. First, there is no sanction for this in the
policy itself. Secondly, it would have the result of placing an ever increasing
value on shorter and shorter periods of extension, depending on how close to a
patient's probable death the extension was obtained. Although….it was very
understandable that a patient and their family and friends might argue for this,
it was not a logical position from a broader NHS perspective.” (para. 44)
However, the appeal panel go on in para. 46 to say:
“However, the Appeal Panel did not accept the Committee's approach to the
meaning of the requirement that life extension should be ‘normally of at least
an additional 3 months, compared to current NHS treatment.’ The Appeal
Panel concluded that the Appraisal Committee was not correct to have read
that as requiring a minimum of an average of three months in absolutely every
case. It would, in compelling circumstances, be open to the Appraisal
Committee to accept an average value of less than three months.”
And they continue in para. 47:
“In deciding what constitutes a compelling circumstance, it would have to be
borne in mind first that all patients to whom the Supplementary Advice might
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be applied are in …a parlous situation. All will be facing the end of life, with
all that that entails. That is not a ‘compelling circumstance’ in itself.
Something over and above the features common to all or many end of life
cases would be required before the Committee could justify accepting a mean
benefit of less than three months. The Supplementary Advice is itself already a
policy dealing with a departure from normal policy in exceptional
circumstances. Clear and strong justification would be required for an
exceptional departure from what is already an exceptional policy, particularly
if the departure is more than nominal. It might be that such compelling
circumstances would almost never be present. Nonetheless, the Committee
was mistaken to have thought that it had no discretion at all to apply the
Supplementary Advice where the mean survival benefit is shown to be less
than three months.”
In para. 48 the Appeal Panel allowed the appeal on this point “in so far as the
Committee should consider whether, exceptionally, a life extension of less
than three months might be acceptable in this case.”
A paper prepared for the NICE board in 2009 drew attention to the issue of
‘exceptionality’ and invited the board to consider the nature of what
“exceptional” might mean (NICE, 2009b; para. 2.7). It does not seem that
clarifications on this are publicly available as yet, but the question of what an
‘exceptional’ case or ‘compelling circumstances’ might be in already
‘exceptional’ and ‘compelling’ circumstances is an interesting one.
5. References/Links to
relevant documents
GlaxoSmithKline Notice of Appeal, March 2009. Available at:
http://www.nice.org.uk/nicemedia/live/11731/44499/44499.pdf
NICE Guidance Executive (2010) Lapatinib for women with previously
treated advanced or metastatic breast cancer
Available at:
http://www.nice.org.uk/nicemedia/live/11731/47060/47060.pdf
NICE (2010) Final Appraisal Determination: Lapatinib for the treatment of
women with previously treated advanced or metastatic breast cancer.
Available at: http://www.nice.org.uk/nicemedia/live/11731/49197/49197.pdf.
NICE, Appeal Hearing on Lapatinib, July 2009. Available at:
http://www.nice.org.uk/nicemedia/live/11731/44808/44808.pdf
NICE (2009a) Final Appraisal Determination: Lapatinib for the treatment of
women with previously treated advanced or metastatic breast cancer.
Available at:
http://www.nice.org.uk/nicemedia/live/11731/43476/43476.pdf
NICE (2009b) Update Report on the Application of the End of Life
Supplementary Advice in Health Technology Appraisals. Available at:
http://www.gserve.nice.org.uk/media/835/8E/ITEM7EndOfLifeTreatments.pdf
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